2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)acetic acid | 1260139-76-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)acetic acid
• 英文别名: 2-(6-chloro-3,4-dihydro-2H-quinolin-1-yl)acetic acid
• CAS: 1260139-76-1
• 化学式: C₁₁H₁₂ClNO₂
• 分子量: 225.675
• InChiKey: CQECJTCDYVIRJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)acetic acid 、 1-Amino-4-[(dimethylsulfamoylamino)methyl]cyclohexane 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(6-chloro-3,4-dihydro-2H-quinolin-1-yl)-N-[4-[(propan-2-ylsulfonylamino)methyl]cyclohexyl]acetamide
  参考文献：
  名称：

  N-Heteroaryl glycinamides and glycinamines as potent NPY5 antagonists

  摘要：

  Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimization efforts are described targeting improvements in potency, microsomal stability, and PK properties. The low microsomal stability and poor PK properties were addressed through the optimization of the sulfonyl urea and replacement of the benzothiazepinone with other N-heteroaryl glycinamides. For example, the analogous benzoxazine glycinamide 2e has improvements in both affinity (human Y5 K-i 4 nM vs 1a 27 nM) and microsomal stability (human CLint 2.5 L/min vs 1a 35 L/min). However the brain penetration (B/P 43/430 nM at 10 mg/kg PO) remained an unresolved issue. Further optimization by decreasing the hydrogen bond donating properties and PSA provided potent and brain penetrant NPY5 antagonists such as 5f (human Y5 K-i 9 nM, B/P 520/840 nM 10 mg/kg PO). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.078
• 作为产物：
  描述：

  6-氯-1,2,3,4-四氢喹啉 在 四丁基溴化铵 、 水 、 potassium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)acetic acid
  参考文献：
  名称：

  N-Heteroaryl glycinamides and glycinamines as potent NPY5 antagonists

  摘要：

  Subtype specific ligands are needed to evaluate the therapeutic potential of modulating the brain's neuropeptide Y system. The benzothiazepine glycinamide 1a was identified as an NPY5 antagonist lead. While having acceptable solubility, the compound was found to suffer from high clearance and poor exposure. Optimization efforts are described targeting improvements in potency, microsomal stability, and PK properties. The low microsomal stability and poor PK properties were addressed through the optimization of the sulfonyl urea and replacement of the benzothiazepinone with other N-heteroaryl glycinamides. For example, the analogous benzoxazine glycinamide 2e has improvements in both affinity (human Y5 K-i 4 nM vs 1a 27 nM) and microsomal stability (human CLint 2.5 L/min vs 1a 35 L/min). However the brain penetration (B/P 43/430 nM at 10 mg/kg PO) remained an unresolved issue. Further optimization by decreasing the hydrogen bond donating properties and PSA provided potent and brain penetrant NPY5 antagonists such as 5f (human Y5 K-i 9 nM, B/P 520/840 nM 10 mg/kg PO). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.078

文献信息

• Heterocyclic derivatives as modulators of ion channels
  申请人：Martinborough Esther

  公开号：US20080027067A1

  公开（公告）日：2008-01-31

  The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及用作离子通道抑制剂的杂环衍生物。该发明还提供了包括本发明化合物的药用可接受组合物，以及使用这些组合物治疗各种疾病的方法。
• Pyrrolidinyl phenyl sulphonamides as modulators of ion channels
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US08163720B2

  公开（公告）日：2012-04-24

  The present invention relates to phenyl sulfonamides useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including for example the treatment of pain.

  本发明涉及苯基磺酰胺，其作为离子通道抑制剂的用途。本发明还提供了包含本发明化合物的药学上可接受的组合物，并提供了使用这些组合物治疗各种疾病的方法，例如治疗疼痛。
• PHENYL SULFONAMIDES AS MODULATORS OF ION CHANNELS
  申请人：Martinborough Esther

  公开号：US20110082117A1

  公开（公告）日：2011-04-07

  The present invention relates to heterocyclic derivatives useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders.

  本发明涉及杂环衍生物，可用作离子通道抑制剂。本发明还提供了包含本发明化合物的药学上可接受的组合物，并提供了使用这些组合物治疗各种疾病的方法。
• PHENYL SULPHONAMIDES AS MODULATORS OF ION CHANNELS
  申请人：Martinborough Esther

  公开号：US20120178713A1

  公开（公告）日：2012-07-12

  The present invention relates to phenyl sulfonamides useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including for example the treatment of pain.

  本发明涉及苯基磺酰胺类化合物，其可用作离子通道抑制剂。本发明还提供了包含本发明化合物的药学上可接受的组合物，并提供了使用该组合物治疗各种疾病的方法，例如用于治疗疼痛。
• Phenyl sulfonamides as modulators of ion channels
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US07799822B2

  公开（公告）日：2010-09-21

  The present invention relates to phenyl sulfonamides useful as inhibitors of ion channels. The invention also provides pharmaceutically acceptable compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various disorders, including for example the treatment of pain.

  本发明涉及苯基磺酰胺，可用作离子通道抑制剂。本发明还提供了包含本发明化合物的药学上可接受的组合物，并提供使用这些组合物治疗各种疾病的方法，例如治疗疼痛。